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The γ-aminobutyric acid type A receptor (GABA (A) receptor) is a membrane protein activated by the neurotransmitter GABA. Structurally, this major inhibitory neurotransmitter receptor in the human central nervous system is a pentamer that can be built from a selection of 19 subunits consisting of α(1,2,3,4,5 or 6), β (1,2 or 3), γ (1,2 or 3), ρ (1,2 or 3), and δ, π, θ, and ε. This creates several possible pentameric arrangements, which also influence the pharmacological and physiological properties of the receptor. The complexity and heterogeneity of the receptors are further increased by the addition of short and long splice variants in several subunits and the existence of multiple allosteric binding sites and expansive ligands that can bind to the receptors. Therefore, a comprehensive understanding of the structure and function of the receptors is required to gain novel insights into the consequences of receptor dysfunction and subsequent drug development studies. Notably, advancements in computational-aided studies have facilitated the elucidation of residual interactions and exploring energy binding, which may otherwise be challenging to investigate. In this review, we aim to summarize the current understanding of the structure and function of GABA (A) receptors obtained from advancements in computational-aided applications. © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Citation

Fatin H Mohamad, Muhamad Arif Mohamad Jamali, Ahmad Tarmizi Che Has. Structure-function Studies of GABA (A) Receptors and Related computer-aided Studies. Journal of molecular neuroscience : MN. 2023 Oct;73(9-10):804-817

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PMID: 37750966

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